Current status of porcine islet xenotransplantation

Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. However, the shortage of islet donors limits its' broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment.

Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization.

This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.